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Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole

Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations....

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Autores principales: Li, Li Ping, Liu, Wei, Liu, Hong, Zhu, Fang, Zhang, Da Zhi, Shen, Hui, Xu, Zheng, Qi, Yun Peng, Zhang, Shi Qun, Chen, Si Min, He, Li Juan, Cao, Xin Ju, Huang, Xin, Zhang, Jun Dong, Yan, Lan, An, Mao Mao, Jiang, Yuan Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438075/
https://www.ncbi.nlm.nih.gov/pubmed/25992630
http://dx.doi.org/10.1371/journal.pone.0126393
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author Li, Li Ping
Liu, Wei
Liu, Hong
Zhu, Fang
Zhang, Da Zhi
Shen, Hui
Xu, Zheng
Qi, Yun Peng
Zhang, Shi Qun
Chen, Si Min
He, Li Juan
Cao, Xin Ju
Huang, Xin
Zhang, Jun Dong
Yan, Lan
An, Mao Mao
Jiang, Yuan Ying
author_facet Li, Li Ping
Liu, Wei
Liu, Hong
Zhu, Fang
Zhang, Da Zhi
Shen, Hui
Xu, Zheng
Qi, Yun Peng
Zhang, Shi Qun
Chen, Si Min
He, Li Juan
Cao, Xin Ju
Huang, Xin
Zhang, Jun Dong
Yan, Lan
An, Mao Mao
Jiang, Yuan Ying
author_sort Li, Li Ping
collection PubMed
description Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells’ self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections.
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spelling pubmed-44380752015-05-29 Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole Li, Li Ping Liu, Wei Liu, Hong Zhu, Fang Zhang, Da Zhi Shen, Hui Xu, Zheng Qi, Yun Peng Zhang, Shi Qun Chen, Si Min He, Li Juan Cao, Xin Ju Huang, Xin Zhang, Jun Dong Yan, Lan An, Mao Mao Jiang, Yuan Ying PLoS One Research Article Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells’ self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections. Public Library of Science 2015-05-19 /pmc/articles/PMC4438075/ /pubmed/25992630 http://dx.doi.org/10.1371/journal.pone.0126393 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Li Ping
Liu, Wei
Liu, Hong
Zhu, Fang
Zhang, Da Zhi
Shen, Hui
Xu, Zheng
Qi, Yun Peng
Zhang, Shi Qun
Chen, Si Min
He, Li Juan
Cao, Xin Ju
Huang, Xin
Zhang, Jun Dong
Yan, Lan
An, Mao Mao
Jiang, Yuan Ying
Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole
title Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole
title_full Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole
title_fullStr Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole
title_full_unstemmed Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole
title_short Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole
title_sort synergistic antifungal activity of berberine derivative b-7b and fluconazole
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438075/
https://www.ncbi.nlm.nih.gov/pubmed/25992630
http://dx.doi.org/10.1371/journal.pone.0126393
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